CAR Cell Therapies for Lupus

CAR cell therapy is a new type of therapy that has been used in cancer and is now in development for potential treatment of lupus and other autoimmune diseases. CAR cell therapies carry a modified protein called a chimeric antigen receptor (CAR). This strategically designed protein can change the way that an immune cell functions in the body. CAR cells can either be made from immune cells that are taken from the patient (autologous cells) or they can be made from cells from a healthy donor (allogeneic cells).

CAR cell therapies are named using the prefix CAR followed by the type of cell that is being modified. Many of the cells currently being tested to treat lupus are a kind of immune cell called a T cell, so they are called CAR T cells. Most of these CAR T cells are programmed to target another kind of immune cell called a B cell. B cells are often overly activated in people with lupus, and this is the type of cell that produces autoantibodies which play key roles in inflammation and organ damage.

There are several different CAR cell therapies possible, using different types of cells. For example, several drug developers are also studying CAR cell therapy using natural killer (NK) cells. Even CAR cell therapies that use the same type of cell are different from one another depending on the specific process used for modifying the cell or the specific CAR inserted into the cell. Therefore, many different strategic approaches are possible to modify the immune system using CAR cell therapies.

CAR cell therapies were first developed to treat blood cancers. They are a potential treatment for lupus because the modified cells have direct access to inflamed tissues in all parts of the body. This allows for more complete and targeted reduction of overly active B cells in lupus. By reducing the cells that cause inflammation, it is hoped that CAR cell therapy can lead to reduced immune system activity and improved quality of life.

The treatment process for CAR cell therapies is intensive and complicated. Currently, CAR cell therapy to treat lupus or other autoimmune conditions is only available through clinical trials. The trials in lupus patients are open to a small number of people with refractory lupus, meaning that they have significant lupus activity that has not responded to standard treatments.

CAR cell therapy requires a multi-step approach, usually involving chemotherapy that temporarily depletes the immune cells necessary to protect the body. People undergoing this process will likely need to stay near the clinical center for several weeks after treatment. This means that there are barriers to receiving CAR cell therapy for many people with lupus. It is possible, however, that when this treatment works, some patients might be in remission for a long time, maybe even for years. Not enough is known yet to guarantee that this will happen, however.

By studying CAR cell therapy in refractory lupus, researchers may be able to control the symptoms for people who are running out of choices for treatment. Researchers may also gain knowledge from these clinical trials that will one day help those with less severe forms of lupus. However, more needs to be understood about the risks, benefits, and optimal ways to give the treatments before people with controllable symptoms should consider this approach.

Phase I Clinical Trials

Phase I clinical trials are the first stage of testing a new drug in humans, primarily focused on safety. These trials typically involve a small group of 20 to 100 participants, usually healthy volunteers, to evaluate how the body processes the drug and identify any side effects. Researchers carefully monitor participants to determine the safest dose and how the drug is absorbed, metabolized, and excreted. While effectiveness is not the main focus at this stage, early signs of how the drug works may emerge. If the drug proves to be safe, it progresses to Phase 2 trials, where its effectiveness is studied in a larger group of patients.

CENTURY THERAPEUTICS (NCT06255028)

The CALiPSO-1 Phase 1 study is testing a new type of cell therapy called CNTY-101, which is made from turning regular cells (like skin or blood cells) back into stem cells, which can then change into almost any type of cell in the body to help repair or replace damaged tissue to see if it can help people with hard-to-treat autoimmune diseases, such as lupus (SLE/lupus nephritis), inflammatory muscle diseases (IIM), and a severe form of scleroderma (DcSSc). CNTY-101 is made from specially engineered natural killer (NK) cells designed to target disease-causing B cells. The study will track side effects, assess the overall safety of the treatment, evaluate how well people tolerate it, identify the safest dosage, and find the best treatment plan for future trials, with or without IL-2.

CULLINAN THERAPEUTICS (NCT06613360)

This Phase 1b study is evaluating CLN-978, a CD19-directed T-cell engager, as a potential treatment for moderate to severe systemic lupus erythematosus (SLE). Unlike traditional CAR-T therapies, CLN-978 is given as a subcutaneous injection and works by redirecting T cells to target and eliminate harmful B cells. The study aims to assess the safety and tolerability of this approach over 48 weeks, with the goal of developing new treatment options for SLE and relapsed or refractory B-cell non-Hodgkin lymphoma.

NKARTA INC. (NCT06557265)

The Ntrust-1 study is a Phase 1 trial evaluating NKX019, an allogeneic CAR Natural Killer (NK) cell therapy, as a potential treatment for lupus nephritis (LN). This therapy is designed to target CD19-positive B cells, which play a role in autoimmune disease. The study aims to assess the safety and tolerability of NKX019 in adults with active LN, monitor side effects and determine the best dosage over a 44-day period.